Venti l ator- associ ated

Compl i cati ons, I ncl udi ng

I nfecti on- rel ated Compl i cati ons
The Way Forward
Marin H. Kollef, MD
INTRODUCTION
Ventilator-associated pneumonia (VAP) is one of the most common infections occur-
ring in mechanically ventilated patients requiring antibiotic administration. Because
VAP has historically been associated with excess morbidity and mortality in critically
ill patients, it has been used as an overall marker of the quality of care associated
with mechanical ventilation. Although recent studies have challenged the association
between VAP and increased mortality, there is greater consensus that VAP is associ-
ated with prolonged durations of mechanical ventilation, increased intensive care
unit (ICU) length of stay, and increased hospital costs.
14
Bekaert and colleagues
5
This work was supported by the Barnes-Jewish Hospital Foundation.
Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
E-mail address: mkollef@dom.wustl.edu
KEYWORDS

VAP

VAC

Pneumonia

ICU
KEY POINTS
Optimizing the care of mechanically ventilated patients is an important goal for health care
providers and hospital administrators.
An easily acquired and reliable marker of medical quality has been elusive for this patient
population.
Ventilator-associated complications (VACs) represent a potential solution to this problem.
VACs can be easily monitored for and obtained, being defined by changes in oxygenation
and/or positive end-expiratory pressure.
The potential also exists to track VACs automatically using hospital informatics systems.
It is important to first establish that VACs are preventable, and not simply markers of
disease severity, to use them as true markers of medical quality for purposes of interinsti-
tutional comparison and reimbursement.
Crit Care Clin 29 (2013) 3350
http://dx.doi.org/10.1016/j.ccc.2012.10.004 criticalcare.theclinics.com
0749-0704/13/$ see front matter 2013 Elsevier Inc. All rights reserved.
estimated that 4.4%of the deaths in the ICUon day 30 and 5.9%on day 60 are attribut-
able to VAP. As opposed to previous studies, these investigators simultaneously
accounted for the time of acquiring VAP, loss to follow-up after ICU discharge, and
the existence of complex feedback relations between VAP and disease severity. Kollef
and colleagues
4
showed, in a matched cohort, that patients with VAP had longer mean
durations of mechanical ventilation (21.8 vs 10.3 days), ICU stay (20.5 vs 11.6 days),
hospitalization(32.6vs 19.5days), andcosts ($99,598vs $59,770) than patients without
VAP.
One of the major clinical issues related to the management of mechanically venti-
lated patients in the ICU is the increasing occurrence of infections, including VAP,
caused by multidrug-resistant (MDR) or extremely drug-resistant (XDR) pathogens.
6
The available evidence suggests that the overall prevalence of nosocomial infections
attributed to MDR and XDR pathogens, as well as the global use of antibiotics in the
hospital setting, is not diminishing despite local and national efforts to curb these
infections.
7,8
Disorders such as tracheobronchitis and sepsis, which often are diag-
nosed in the presence of nosocomial pneumonia, seem to be more common, contrib-
uting, at least in part, to the increasing use of antibiotics in the ICU.
9
VAP is recognized
to be among the most common infections associated with MDR and XDR bacteria
including Pseudomonas aeruginosa, Acinetobacter species, and Klebsiella pneumonia
carbapenemasecontaining Enterobacteriaceae.
819
The recent recognition of Enter-
obacteriaceae containing the NDM1 gene in multiple continents raises the possibility
of endemic spread of common enteric bacteria possessing resistance to all currently
available antibacterial agents.
11
The major concern related to the emergence of MDRand XDRpathogens as a cause
of VAP is the inability to empirically treat these infections when they are initially sus-
pected. Inappropriate initial antimicrobial therapy, defined as an antimicrobial regimen
that lacks in vitro activity against the isolated organism(s) responsible for the infection,
has been associated with excess mortality in patients with serious infections, including
VAP and severe sepsis.
10,16,2023
This is largely related to increasing bacterial resis-
tance to antibiotics as a result of their greater use and the limited availability of newer
agents.
6,17
Escalating rates of antimicrobial resistance lead many clinicians to empiri-
cally treat critically ill patients with presumed infection with a combination of broad-
spectrumantibiotics, which can further perpetuate the cycle of increasing resistance.
17
Inappropriate initial antimicrobial therapy can, conversely, lead to treatment failures
and adverse patient outcomes.
18,22
Moreover, the limited diversity of available antimi-
crobial agents has created a clinical situation in which patients are repetitively exposed
to the same class of antibiotic, or, in some circumstances, the same agent, resulting in
an increased risk of treatment failure and mortality.
19
Therefore, the broader concern
for all intensivists is how to limit the emergence and spread of MDR/XDR pathogens,
as well as the infections associated with these pathogens.
A recent international point prevalence ICU study found the lungs to be the most
common site of infection, accounting for 64% of infections, followed by the abdomen
(20%), the bloodstream (15%), and the renal tract/genitourinary system (14%).
9
Despite important geographic variations, Enterococcus faecium, Staphylococcus
aureus, K pneumoniae, Acinetobacter baumannii, P aeruginosa, and Enterobacter
species (ESKAPE) pathogens constitute more than 80% of VAP episodes.
9,15
Their
clinical importance relies on their virulence and ability to develop mechanisms confer-
ring decreased susceptibility to antimicrobials, increasing inappropriate therapy and
negatively affecting the outcomes of patients in the ICU. These studies highlight the
overall importance of pulmonary infections as a major cause of morbidity and antibi-
otic use in the ICU. However, given concerns about current diagnostic criteria for VAP,
Kollef 34
especially for assessing the clinical impact of infection prevention or quality-
improvement programs on patient outcomes, other indicators of ICU care quality
have been explored.
24,25
PROBLEMATIC DEFINITION OF VAP
Clinical criteria are known to be nonspecific for the diagnosis of nosocomial pneu-
monia, including VAP. Clinical findings such as fever, leukocytosis, and purulent
secretions occur with other noninfectious pulmonary conditions such as atelectasis,
pulmonary contusion, and acute respiratory distress syndrome (ARDS), and therefore
lack specificity for the diagnosis of VAP.
2629
Chest radiographs can similarly be
nonspecific for the diagnosis of nosocomial pneumonia. Wunderink and colleagues
30
found that no roentgenographic sign correlated well with the presence of pneumonia
in mechanically ventilated patients. The presence of air bronchograms was the only
roentgenographic sign that correlated with autopsy-verified pneumonia, correctly pre-
dicting 64%of cases. The most frequently used clinical diagnosis of VAP has tradition-
ally required the presence of a new or progressive consolidation on chest radiology
plus at least 2 of the following clinical criteria: fever greater than 38

C, leukocytosis
or leukopenia, and purulent secretions. This definition has been supported by several
medical specialty groups,
31,32
despite the lack of specificity of these criteria.
2730
The Centers for Disease Control and Prevention (CDC)/National Healthcare Safety
Network (NHSN) has established a clinical definition for the presence of probable
nosocomial pneumonia including VAP.
33
However, these diagnostic criteria have
not been validated and at least 1 study found that decision making using these criteria
was not accurate, potentially resulting in the withholding of antibiotics in 16% of
patients diagnosed with VAP by bronchoalveolar lavage (BAL).
34
We recently
compared the observed rates of VAP when using the CDC/NHSN surveillance method
versus the American College of Chest Physicians (ACCP) clinical criteria.
35
Over 1
year, 2060 patients required mechanical ventilation for greater than 24 hours and
were prospectively evaluated. Of these, 83 patients (4%) had VAP according to the
ACCP criteria, compared with 12 patients (0.6%) using the CDC/NHSN surveillance
method. The corresponding rates of VAP were 8.5 versus 1.2 cases per 1000 ventilator
days, respectively. Agreement of the 2 sets of criteria was poor (k statistic, 0.26).
Quantitative lower respiratory tract cultures were positive in 88% of patients in the
ACCP group and 92% in the NHSN group.
35
Others have noted that surveillance rates of VAP are decreasing, whereas clinical
diagnoses of VAP and tracheobronchitis, as well as antibiotic prescribing, remain
prevalent.
36
External reporting pressures may be encouraging stricter interpretation
of subjective signs that can cause an artifactual lowering of VAP rates. The result is
that it is almost impossible to disentangle the relative contribution of quality-
improvement efforts in the ICU versus surveillance effects as explanations for the
currently observed low VAP rates.
36
Given the limitations of clinical criteria for estab-
lishing the diagnosis of VAP, alternative methods have been pursued. Torres and
colleagues
37
used quantitative cultures of respiratory specimens obtained by BAL,
protected BAL (pBAL), protected specimen brush, and tracheobronchial aspirate
(TBA), which were compared with histology of lung biopsy samples to establish the
diagnosis of VAP. Sensitivities for the diagnosis of VAP ranged from 16% to 37%
when only histologic reference tests were used, whereas specificity ranged from
50% to 77%. When lung histology of guided or blind specimens and microbiology
of lung tissue were combined, all quantitative diagnostic techniques achieved higher,
but still limited, diagnostic yields (sensitivity 43%83%; specificity 67%91%).
37
Ventilator-associated Complications 35
Similar diagnostic accuracy has been shown by other investigators using histologic
criteria as a reference standard, suggesting that quantitative cultures of lower respira-
tory secretions may be of limited value.
27,3845
To simplify the technical requirements for establishing a microbiologic diagnosis of
VAP, Riaz and colleagues
46
compared nonquantitative and quantitative respiratory
secretion cultures for the diagnosis of VAP. These investigators found that nonquan-
titative culture of BAL was good at ruling out the presence of VAP but was poor at
establishing the presence of VAP because of the low specificity of the test. Despite
the limited overall accuracy of quantitative lower respiratory tract cultures for the diag-
nosis of VAP, the clinical use of such cultures has been associated with less overall
antibiotic use,
4750
which presumably results from clinicians having greater confi-
dence in ruling out VAP with negative quantitative culture results. Similar reductions
in the duration of antibiotic therapy prescribed for clinically suspected VAP have
been shown using serum procalcitonin thresholds, Clinical Pulmonary Infection Score
(CPIS) values, and targeted protocols.
5154
Given that VAP surveillance is time consuming, potentially less accurate than clin-
ical/microbiologic criteria,
34,35
and the use of quantitative lower respiratory tract
cultures for the establishment of VAP is not universally performed, the CDCEpicenters
Program(CDC-PEP) has recently supported efforts to shift ICUsurveillance away from
VAP. Instead, the CDC-PEP has focused on the occurrence of complications in
general that might circumvent the VAP definitions subjectivity and inaccuracy, facili-
tate electronic assessment, make interfacility comparisons more meaningful, and
encourage broader prevention strategies. Ventilator-associated complications
(VACs) was selected as a more general marker and was defined by sustained
increases in patients ventilator settings after a period of stable or decreasing support
(Box 1).
The use of VAC as an outcome predictor was examined in a recent CDC-PEP study
of 597 mechanically ventilated patients.
55
These investigators found that 9.3% of their
study population developed VAP (8.8 per 1000 ventilator days) whereas 23% had
a VAC (21.2 per 1000 ventilator days). Compared with matched controls, both VAP
and VAC prolonged days to extubation (5.8, 95% confidence interval [CI] 4.28.0
and 6.0, 95% CI 5.17.1 respectively), days to ICU discharge (5.7, 95% CI 4.27.7
and 5.0, 95% CI 4.15.9), and days to hospital discharge (4.7, 95% CI 2.67.5 and
3.0, 95% CI 2.14.0). VAC was associated with increased mortality (odds ratio [OR]
2.0, 95% CI 1.33.2) but VAP was not (OR 1.1, 95% CI 0.52.4). VAC assessment
was also faster (mean 1.8 minutes vs 39 minutes per patient). Both VAP and VAC
events were predominantly attributable to pneumonia, pulmonary edema, ARDS,
and atelectasis. The investigators concluded that screening for VAC captures a similar
set of complications to traditional VAP surveillance but is faster, more objective, and
potentially a superior predictor of clinical outcomes.
Building on their experience with VAC, the CDC-PEP has begun to evaluate a new
streamlined surveillance definition for VAP (sVAP) (Table 1) based on their experience
with VAC. The same investigators retrospectively compared surveillance time, repro-
ducibility, and outcomes for streamlined versus conventional surveillance definitions
of VAP among medical and surgical patients on mechanical ventilation in 3 university
hospitals.
56
Application of the streamlined definition was faster (mean 3.5 minutes vs
39.0 minutes per patient) and more objective than the conventional definition. On
multivariate analysis, the streamlined definition predicted increases in ventilator
days, intensive care days, and hospital mortality as effectively as conventional surveil-
lance. Although sVAP does not necessarily reflect the presence of bacterial pneu-
monia, it is hoped that this marker will allow quality-improvement efforts to be more
Kollef 36
accurately assessed across time periods and institutions compared with the tradi-
tional use of VAP as a quality indicator.
57
However, neither VAC or sVAP have been
evaluated in terms of potentially modifying antibiotic consumption or reducing the
emergence of antibiotic-resistant bacteria in the ICU setting.
An accompanying editorial from the CDC-PEC suggested that the NHSN is
committed to completing and implementing new quality criteria for critically ill patients
in the form of VAC and IVAC (see Box 1).
58
These streamlined quality criteria will
undergo a period of review from various critical care groups and societies (Society
of Critical Care Medicine, American Association of Respiratory Care, ACCP, American
Thoracic Society, and American Society of Critical Care Nurses) before their expected
acceptance and implementation by the National Quality Forum and the Centers for
Medicare & Medicaid Services. With input from these key constituents, NHSN is
prepared to make changes that will maximize reliable case identification, be respon-
sive to newscientific findings, and simplify implementation through use of advances in
health information technology, while maintaining clinical and epidemiologic credibility
through partnerships with key providers and state health departments. The hope is
that implementation of these new surveillance criteria will allow the quality of medical
care to be more accurately assessed in the ICUsetting. However, to accomplish these
goals, most VACs and IVACs have to be shown to be preventable to effectively link
them to health care quality.
BUNDLES FOR QUALITY IMPROVEMENT AND THE PREVENTION OF VAP
More than a decade ago, an education-based program at Barnes-Jewish Hospital
directed toward respiratory care practitioners and ICU nurses was developed by
a multidisciplinary task force to highlight correct practices for the prevention of
VAP.
59
Each participant was required to take a preintervention test before reviewing
a study module and an identical postintervention test after completion of the study
module. Following implementation of the education module, the rate of VAP
decreased to 5.7 per 1000 ventilator days from 12.6 per 1000 ventilator days.
59
The
cost savings secondary to the decreased rate of VAP for the 12 months following
the intervention was estimated to be greater than $400,000. This educational protocol
was then implemented across the 4 largest hospitals in the local health care system.
60
VAP rates for all 4 hospitals combined decreased by 46%, from 8.75/1000 ventilator
days in the year before the intervention to 4.74/1000 ventilator days in the 18 months
following the intervention (P<.001). Statistically significant decreased rates were
observed at the pediatric hospital and at 2 of the 3 adult hospitals. No significant
change in VAP rates was seen at the community hospital with the lowest rate of study
module completion among respiratory therapists (56%). In addition to showing the
effectiveness of a bundle for VAP prevention, these studies highlight the importance
of compliance with the elements of the bundle to ensure its success. This same
education-based bundle package has also been successfully used in the ICUs of
a hospital in Thailand.
61
Lansford and colleagues
62
also developed a simple bundle for the prevention of
VAP in patients with trauma, focusing on head of bed elevation, oral cleansing with
chlorhexidine, a once-daily respiratory therapistdriven weaning attempt, and conver-
sion of nasogastric to orogastric feeding tubes. Implementation of this bundle was
associated with a significant reduction in the rate of VAP. Elements of this bundle
have also been shown to be effective in other surgical/trauma units at Barnes-
Jewish Hospital.
63
However, compliance with infection control protocols often wanes
over time and can be significantly influenced by staffing levels in the ICU.
64
Some
Ventilator-associated Complications 37
Box 1
Criteria for VACs, infection-related VACs (IVACs), possible VAP, and probable VAP proposed by
the CDC-PEP
a
VAC
Patient has a baseline period of stability or improvement on the ventilator, defined by 2 or
more calendar days of stable or decreasing FiO
2
or PEEP. Baseline FiO
2
and PEEP are defined
by the minimum daily FiO
2
or PEEP measurement during the period of stability or
improvement.
After a period of stability or improvement on the ventilator, the patient has at least 1 of the
following indicators of worsening oxygenation:
1. Minimum daily FiO
2
values increase greater than or equal to 0.20 (20 points) more than
baseline and remain equal to or more than that increased level for 2 or more calendar
days
2. Minimum daily PEEP values increase greater than or equal to 3 cm H
2
O more than baseline
and remain equal to or more than that increased level for 2 or more calendar days
IVAC
On or after calendar day 3 of mechanical ventilation and within 2 calendar days before or after
the onset of worsening oxygenation, the patient meets both of the following criteria:
1. Temperature greater than 38

C or less than 36

C, or white blood cell count greater than or

equal to 12,000 cells/mm
3
or less than or equal to 4000 cells/mm
3
2. A new antimicrobial agent(s) is started, and is continued for greater than or equal to 4
calendar days
Possible VAP
On or after calendar day 3 of mechanical ventilation and within 2 calendar days before or after
the onset of worsening oxygenation, 1 of the following criteria is met:
1. Purulent respiratory secretions (from 1 or more specimen collections)
a. Defined as secretions from the lungs, bronchi, or trachea that contain more than 25
neutrophils and less than 10 squamous epithelial cells per low-power field
b. If the laboratory reports semiquantitative results, those results must be equivalent to the
quantitative thresholds presented earlier
2. Positive culture (qualitative, semiquantitative, or quantitative) of sputum, endotracheal
aspirate, BAL, lung tissue, or protected specimen brushing
Probable VAP
On or after calendar day 3 of mechanical ventilation and within 2 calendar days before or after
the onset of worsening oxygenation, 1 of the following criteria is met:
1. Purulent respiratory secretions (from 1 or more specimen collections and defined as for
possible VAP)
And 1 of the following:
a. Positive culture of endotracheal aspirate, greater than or equal to 10
5
CFU/mL, or
equivalent semiquantitative result
b. Positive culture of BAL, greater than or equal to 10
4
CFU/mL, or equivalent
semiquantitative result
c. Positive culture of lung tissue, greater than or equal to 10
4
CFU/mL, or equivalent
semiquantitative result
d. Positive culture of protected specimen brush, greater than or equal to 10
3
CFU/mL, or
equivalent semiquantitative result
Kollef 38
institutions have used computerized flow sheets and quality rounding checklists in the
ICU to improve compliance with care measures involved in the prevention of VAP, as
well as other complications (eg, deep vein thrombosis, stress ulcer formation).
6567
Berenholtz and colleagues
68
implemented a statewide multifaceted intervention to
improve compliance with 5 evidence-based recommendations for mechanically venti-
lated patients and to prevent VAP. One-hundred and twelve ICUs reporting 3228 ICU
months and 550,800 ventilator days showed the VAP rate to have decreased from
a mean of 6.9 cases per 1000 ventilator days at baseline to a mean of 3.4 cases per
1000 ventilator days at 16 to 18 months after implementation.
68
Rello and colleagues
69
conducted a VAP prevention study in 5 Spanish adult ICUs
focusing on 5 evidence-based measures (avoidance of ventilator circuit changes
unless clinically indicated, use of sedation control protocols, strict hand hygiene,
oral care with chlorhexidine, intracuff pressure control of the endotracheal tube).
Despite modest compliance with these interventions that varied between 16.4%
(oral care) and 34.0%(no circuit changes), the prevention intervention achieved reduc-
tions in VAP rates, ICU length of stay, and duration of mechanical ventilation.
Bouadma and colleagues
70
published their experience with a multimodal compre-
hensive intervention strategy for VAP prevention with a strong emphasis on process
control. This French intervention included a multidisciplinary task force, an educa-
tional session, direct observations with performance feedback, technical improve-
ments, and scheduled reminders. Eight evidence-based bundled interventions were
systematically rolled out and used, including hand hygiene, preferably alcohol-
based hand-rubbing; glove and gown use for endotracheal tube manipulation; back-
rest elevation of 30

to 45

; tracheal cuff pressure maintenance greater than 20 cm

H
2
O; use of orogastric tubes; avoidance of gastric overdistension; oral hygiene with
chlorhexidine; and elimination of nonessential tracheal suction. The investigators
carefully monitored compliance with process indicators and VAP rates over the study
period. Compliance assessment consisted of five 4-week periods (before the interven-
tion and at 1, 6, 12, and 24 months thereafter). Compliance with procedures such as
hand hygiene or wearing gloves and gowns for endotracheal tube handling were
already high at study entry and remained so. Other procedures such as backrest
elevation or correct tracheal cuff pressure maintenance were low and did not increase
until the introduction of 2 prompts. Overall quality improvement, measured by a contin-
uous increase in compliance with the 8 prevention measures, resulted in a 51%reduc-
tion of VAP rates.
70
Bouadma and colleagues focused on process control rather than outcome mea-
sure for sustained practice improvement and benchmarking, which is a compelling
2. One of the following (without requirement for purulent respiratory secretions):
a. Positive pleural fluid culture (specimen obtained during thoracentesis or initial
placement of chest tube and not from an indwelling chest tube)
b. Positive lung histopathology
c. Positive diagnostic test for Legionella spp
d. Positive diagnostic test on respiratory secretions for influenza virus, respiratory syncytial
virus, adenovirus, parainfluenza virus
Abbreviations: CFU, colony-forming units; FiO
2
, fraction of inspired oxygen; PEEP, positive end-
expiratory pressure.
a
Note that only VAC and IVAC are intended for public reporting.
Ventilator-associated Complications 39
approach in the light of the unsettled dilemma of VAP definitions and the impact of
case mix.
71
The main advantage of such an approach is the objectivity of the process
elements, which can more accurately be quantified than VAP. In addition, these same
investigators compared VAP rates during a 45-month baseline period and a 30-month
intervention period in a cohort of patients who received mechanical ventilation for
greater than 48 hours.
72
Baseline and intervention VAP rates were 22.6 and 13.1 total
VAP episodes over total mechanical ventilation duration per 1000 ventilation-days,
respectively (P<.001). These cumulative data support the use of targeted approaches
for the reduction of VAP despite the limitations of the criteria used for defining VAP.
They also highlight the importance of VAP as a quality indicator despite the
Table 1
Comparison of conventional and streamlined surveillance definitions for VAP
Conventional Definition Streamlined Definition
Radiology Two or more serial chest
radiographs with at least 1 of
the following:
Two or more serial chest
radiographs with at least 1 of
the following:
1. New or progressive and
persistent infiltrate
1. New or progressive and
persistent infiltrate
2. Consolidation 2. Consolidation
3. Cavitation 3. Cavitation
Systemic signs (at least 1) 1. Fever (>38

C or >100.4

F) 1. Fever (>38

C or >100.4

F)
2. Leukopenia (<4000
WBC/mm
3
) or leukocytosis
(12 000 WBC/mm
3
)
2. Leukopenia (<4000
WBC/mm
3
) or leukocytosis
(12000 WBC/mm
3
)
3. For adults 70 years old,
altered mental status with
no other recognized cause

Pulmonary signs (at least 2) 1. New onset of purulent

sputum, or change in
character of sputum, or
increased respiratory
secretions, or increased
suctioning requirements
1. 25 neutrophils per low-
power field on Gram stain
of endotracheal aspirate
or bronchoalveolar lavage
specimen
2. Worsening gas exchange
(eg, desaturations,
increased oxygen
requirements, or increased
ventilator demand)
2. 2 days of stable or
decreasing daily minimum
PEEP followed by an
increase in daily minimum
PEEP of 2.5 cm H
2
O,
sustained for 2 calendar
days; or 2 days of stable
or decreasing daily
minimum FiO
2
followed by
an increase in daily
minimum FiO
2
of 0.15
points, sustained for 2
calendar days
3. New-onset or worsening
cough, or dyspnea, or
tachypnea

4. Rales or bronchial breath

sounds

Abbreviation: WBC, white blood cell.

Kollef 40
abovementioned limitations. It will be crucial to conduct similar studies using VAC or
IVACas the quality end point to determine whether similar benefits in outcomes can be
achieved.
SELECTING PROCESS ELEMENTS TO INCLUDE IN VAP PREVENTION BUNDLES
The Institute for Healthcare Improvement (IHI) has put forward the simplest venti-
lator bundle, consisting of 4 evidence-based practices to improve the outcomes
of mechanical ventilation: (1) peptic ulcer disease prophylaxis, (2) deep venous
thrombosis prophylaxis, (3) elevation of head of the bed, and (4) daily sedation vaca-
tion and assessment of readiness to wean.
73
Only 2 of these bundle elements
(elevation of the head of the bed and sedation vacations) have been specifically
evaluated as VAP prevention measures. Despite methodological flaws, a recent
systematic review identified 4 peer-reviewed studies that assessed in various
degrees the effect of implementing the IHI ventilator bundle on the incidence of
VAP.
74
In these studies, the incidence of VAP decreased from the range of 2.7 to
13.3 cases to 0.0 to 9.3 cases per 1000 ventilator days. In addition, 2 of the 4 studies
noted a directional decline in the average ICU length of stay. The IHI bundle
approach to VAP prevention, although attractively simple on the surface, may
represent only an incremental first, and seemingly sensible, step to translating
evidence into practice, the impact of which nevertheless remains unknown. The
investigators of this review also concluded that the IHI VAP bundle and other seem-
ingly sensible approaches to VAP prevention need to be examined for their clinical
effectiveness and cost-effectiveness, particularly because new technologies or
prevention strategies coming to market will require evaluation of their comparative
effectiveness.
7577
Other investigations have used more targeted elements in their bundles specifically
aimed at the prevention of VAP.
5961
As previously noted, Bouadma and colleagues
70
implemented a rigorous bundle with 8 evidence-based elements directly linked to the
prevention of VAP. More recently, Heimes and colleagues
78
performed a retrospective
study examining 696 consecutive ventilated patients in a level 1 trauma center to eval-
uate a VAP prevention bundle with 7 elements (elevate head of bed 30

or higher
unless contraindicated; twice-daily oral cleansing with chlorhexidine; daily respiratory
therapydriven attempt to liberate from mechanical ventilation; nasogastric tubes
replaced with orogastric tubes; sedation held and monitored daily to allow patients
to follow commands; stress gastritis prophylaxis with H
2
blockers or proton pump
inhibitors; hand washing by health care personnel). Three time periods were assessed:
pre-VAP bundle implementation, VAP bundle implementation, and a subsequent time
period of VAP bundle enforcement. During the pre-VAP bundle period, 5.2 cases of
VAP occurred per 1000 days of ventilator support compared with 2.4/1000 days
(P5.172) and 1.2/1000 days (P5.085) in the implementation and enforcement
periods, respectively. However, when all trauma patients were included, regardless
of head Abbreviated Injury Score (AIS) score, the difference in the rate of VAP was
statistically significant in the enforcement period, but not in the implementation period,
compared with the pre-VAP bundle period (P5.014 and .062, respectively). In
contrast with the study by Rello and colleagues,
60,69,70
this study supports the need
for strict enforcement or compliance with VAP bundles to maximize their successful
implementation.
One of the main advantages of bundled approaches for the prevention of VAP is
their simplicity and, as a result, their cost-effectiveness. VAP prevention programs
Ventilator-associated Complications 41
have been successfully implemented in developing countries with limited resource
expenditures.
61,79
The implementation of VAP preventive measures grouped into
bundles is a strategy that has consistently been shown to improve effectiveness,
because the combined use of interventions is expected to achieve better outcomes
than when interventions are implemented individually.
8083
The measures that
compose a bundle should be chosen based on the available scientific evidence and
the expected resource availability at the local hospital level. Even when compliance
with the bundle is not fully achieved, a reduction in the incidence of VAP is
possible.
69,82
Similar bundles intended to prevent VACs or IVACs should be validated
in prospective studies.
Box 2
SMART approach to quality control
Specific quality-improvement interventions
Use evidence-based bundle elements
Ensure that local resources are capable of supporting selected bundle elements
Do not become bound to any single bundle element if it is ineffective or impractical to
implement
Measurable outcome
Focus on compliance with process elements
Select limited but clinically relevant outcome measures (eg, VAP incidence, antibiotic use,
duration of mechanical ventilation)
Guard against reporting biases, especially when using before-after or time-series
methods
Achievable program
Target 1 problem or outcome at a time
Do not overreach local resource capability
Develop a local approach to quality improvement that can be applied to subsequent
problems or outcomes
Relevant quality-improvement program
Target problems or outcomes that have direct clinical significance and consequences to
patient care (eg, improved compliance with sedation holiday protocols or infection control
protocols)
Update quality-improvement programs as new information, technology, or resources
become available
Use periodic reviews of all quality-improvement programs by unbiased individuals to
evaluate their success and cost-effectiveness
Time-bound program
Use discrete time periods for the implementation and evaluation of each quality-
improvement program
Develop objective parameters to determine whether quality-improvement interventions
should continue, be modified, or be discontinued
Avoid having quality-improvement programs in place without definite periods of
reevaluation
Kollef 42
SPECIFIC, MEASURABLE, ACHIEVABLE, RELEVANT, TIME-BOUND APPROACHES FOR
QUALITY IMPROVEMENT AND THE PREVENTION OF COMPLICATIONS IN THE ICU
Evidence-based interventions are available to reduce the occurrence of VAP, espe-
cially when these interventions are bundled together.
5961,70
To increase the likeli-
hood of success, clinicians and administrators should follow a specific,
measurable, achievable, relevant, time-bound (SMART) approach for the
implementation of such quality-improvement efforts (Box 2, Fig. 1).
84
Process-
improvement initiatives in the hospital should choose specific objectives that
precisely define and quantify desired outcomes, such as reducing the rate of VAP
by 25% or improving compliance with specific processes (eg, compliance with iden-
tifiable VAP prevention interventions to a predetermined goal level). Such efforts
should avoid unrealistic objectives, such as attempting to completely eliminate
VAP or VACs, which could result in biased underreporting of VAP, or other compli-
cations, to meet the desired goal. A practical process improvement should be
implemented in a way that allows both measurement of the outcome (VAP, VAC,
IVAC, sVAP) and staff adherence to the elements making up the bundle for the
process-improvement project. All objectives should be achievable and relevant by
engaging stakeholders and empowering them to select specific tactics and steps
for implementation. Nurses, respiratory therapists, and other stakeholders are in
the best position to identify the preventive tactics that are achievable within their
busy ICUs. Begin with simple, cost-effective tactics. Anticipate the need to add
more tactics or bundle elements to achieve the desired process implementation
and targeted infection/complication rates, and consider the use of certain measures
designed to enforce the use of the prevention or quality-improvement program
(Box 3).
All process-improvement efforts should be periodically reviewed to assess compli-
ance with their elements and sustained ability to achieve targeted goals, and to intro-
duce advances in technology or behavioral science techniques. Bouadma and
colleagues
70,72
showed the ability of such rigorous methods to produce sustained
VAP rate decreases in the long term. However, these investigators also showed that
VAP rates remained substantial at their institution despite high compliance with
Fig. 1. A SMART program for process improvement and quality control.
Ventilator-associated Complications 43
preventive measures, suggesting that elimination of VAP, or other VACs, may be an
unrealistic goal. Therefore, the focus of such quality-improvement efforts should be
process driven to maximize the benefits of available hospital resources for the desired
goal (eg, reduced occurrence of VAP or VACs).
Box 3
Bundle elements for a mechanical ventilation quality program
Mandatory elements
Strict hand disinfection before patient contacts
Use of noninvasive mask ventilation when possible
Orotracheal intubation preferred (when tracheal intubation is necessary)
Orogastric intubation preferred for gastric access
Appropriate use of analgesia and sedation (daily spontaneous awakening trials when stable)
Daily spontaneous breathing trials (in conjunction with daily spontaneous awakening trials)
Use of checklists or computerized order sets to optimize bundle compliance
Adequate ICU staffing
Avoidance of unplanned extubations and reintubations
Deep vein thrombosis prophylaxis
Gastrointestinal bleeding prophylaxis
Semierect positioning unless contraindicated because of hemodynamics (eg, shock) or
therapeutics (extracorporeal membrane oxygenation)
Avoid ventilator circuit changes unless clinically indicated
Early use of physical therapy and mobilization
Other elements for bundle consideration
Avoidance of patient transports unless clearly clinically indicated
Use of closed endotracheal suctioning
Subglottic secretion drainage
Adequate endotracheal tube cuff pressure
Oral chlorhexidine
Appropriate nutritional support (to include optimal delivery route)
Glucose control
Pressure sore avoidance strategy in place
Enforcement measures
Computerized order sets for bundle elements
Use of rounding checklists
Compliance assessments using random surveillance or observation periods
Distribution of report cards and infection rates
Involvement of hospital leadership in the review of prevention program outcomes
Scheduled in-services, educational briefings, and town hall sessions to review procedures,
outcomes, and barriers to successful bundle implementation
Kollef 44
SUMMARY
Given the rising costs of health care and limited government budgets, process
improvement, safety, and quality should be hardwired into the culture of hos-
pitals, and this is becoming increasingly evident as more institutions are adopting
Toyota-inspired quality management strategies to improve quality as well as to reduce
hospital costs.
85
Moreover, until more objective surveillance end points, such as
sVAP, VAC, or IVAC, are developed and validated, it will be difficult to compare
quality-improvement efforts across sites or to know what levels of improved medical
care (eg, zero VAP or VAC rates) can be achieved.
Health care providers and hospital administration should strive to provide the high-
est level of medical care possible. Nowhere is this more important than high-intensity
resource areas such as the ICU. Intensivists, critical care nurses, and other support
personnel will continue to be challenged to keep pace with rapidly advancing changes
in medical care and technology. The use of a simplified quality indicator, such as VAC
or IVAC, holds the promise of allowing quality to be surveyed over time and across
centers. However, it is imperative that such markers of quality first be validated as rep-
resenting preventable events that can be intervened on.
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